Pcol

• Pharmacology is divided into two main branches: Pharmacodynamics and Pharmacokinetics
• Pharmacodynamics focuses on "what the drug does to the body" and covers the mechanism of action of drugs
• Pharmacokinetics focuses on "what the body does to the drug" and covers biopharmaceutics
• Mechanisms of drug action can be categorized into two main types: Non-targeted protein mediated mechanism and Target protein mediated mechanism
• Non-targeted protein mediated mechanism includes Colligative mechanism, Chemical reaction, and Counterfeit incorporation mechanism
• Colligative mechanism involves drugs acting on osmotic pressure, like MgSO4 acting as a purgative targeting the osmotic pressure in the GIT
• Chemical reaction mechanisms include Neutralization (e.g. Antacid), Chelation (e.g. Deferoxamine for iron toxicity), and others (e.g. CN + Na thiosulfate for cyanide toxicity)
• Counterfeit incorporation mechanism involves drugs structurally similar to biological chemicals being incorporated into cellular components, altering their function (e.g. Flucytosine inhibiting DNA and RNA synthesis)
• Target protein mediated mechanism requires drugs to target a specific protein to exert their pharmacologic effect
• Sites of drug action include target proteins such as structural proteins and regulatory proteins
• Structural proteins like Microtubules are important sites of action for drugs that inhibit microtubule synthesis or spindle protein (e.g. Griseofulvin, Vinca alkaloids)
• Regulatory proteins mediate the transmission of endogenous chemical signals and include transports or channels, carrier molecules, enzymes, and receptors
• Transport proteins like Voltage-gated Na channel are targeted by drugs such as local anesthetics (e.g. CBZ, Phenytoin)
• Carrier molecules like Na+ K+ ATPase pump are targeted by drugs like Digitalis glycosides (e.g. Digoxin for heart failure)
• Enzymes like Xanthine oxidase are targeted by drugs such as Allopurinol for chronic gout
• Receptors are functional macromolecular components of cells with specific configurations that interact with drugs
• Receptors must exhibit specificity, selectivity, affinity, and intrinsic activity for drugs to act on them
• Types of receptors include Type I receptor (ionotropic receptor) and Type II receptor (G-protein linked receptor)
• Type I receptors control movement of ions and include examples like GABA receptors and Nicotinic receptors
• Type II receptors modulate production of intracellular second messengers and include examples like Cyclic Adenosine Monophosphate (CAMP) and Cyclic Guanosine Monophosphate (CGMP)
• Increase in cAMP is not beneficial in the treatment of hypertension because cAMP causes contraction in the heart, leading to an increase in blood pressure
• Increase in cGMP is beneficial in the treatment of hypertension as it causes relaxation in the blood vessels and vasodilation, which decreases blood pressure
• Phosphatidyl choline is converted by the enzyme phospholipase C into IP3 and DAG, leading to an increase in calcium ion responsible for the contraction effect
• Examples of G-proteins:

  • Gs stimulates adenylyl cyclase, increasing cAMP, activated by receptors for Glucagon, Histamine, Serotonin, and blocked by Cholera toxin
  • Gi inhibits adenylyl cyclase, decreasing cAMP, blocked by Pertussis toxin, leading to a decrease in heart rate
  • Gq increases IP3 and DAG, leading to an increase in calcium ion and contraction, activated by receptors for prostanoid
• Examples of Type II receptors:

  • Alpha receptors
  • Beta receptors
  • Muscarinic receptors
• Type III receptor is Tyrosine Kinases-linked receptor, involving tyrosine kinase that catalyzes phosphorylation of tyrosine residues to modulate biochemical processes
• Type IV receptor is Gene Transcription-linked receptor located in the nucleus or cytosol, involved in DNA replication, transcription, and translation
• Drugs that act on Type IV receptors include Corticosteroids, Mineralocorticoids, Sex steroids, Vitamin D, and Thyroid hormone
• Autonomic Nervous System is divided into Central Nervous System and Peripheral Nervous System
• Central Nervous System includes the brain and spinal cord, responsible for processing sensory information, reflex activities, and controlling involuntary movements
• Peripheral Nervous System consists of sensory neurons, motor neurons, and enteric nervous system, responsible for carrying nerve impulses towards and away from the brain
• Anatomy of Neurons:

  • Neurons are the basic unit of the nervous system
  • Dendrites receive stimuli
  • Nucleus processes stimuli
  • Cell body (soma)
  • Axon sends stimuli
  • Synapse is the space between two neurons
• Cranial Nerves:

  I. Olfactory Sensory

  II. Optic Sensory

  III. Occulomotor Motor

  IV. Trochlear Motor

  V. Trigeminal Mixed

  VI. Abducens Motor

  VII. Facial Mixed

  VIII. Vestibulocochlear Sensory

  IX. Glossopharnygeal Mixed

  X. Vagus Mixed

  XI. Spinal Motor

  XII. Hypoglossal Motor
• Subtypes of Efferent Division:

  1. Enteric

  2. Somatic

  3. Autonomic
• Enteric Nervous System is located in the walls of the GIT, activated by diarrhea, and innervated by Myenteric Plexus and Submucous Plexus
• Somatic Nervous System is concerned with consciously controlled functions like movement and posture
• Autonomic Nervous System is largely autonomous, not under direct conscious control, and concerned with visceral functions like cardiac output and digestion
• Autonomic Pathway:

  • Preganglionic nerve fiber terminates and synapses in an autonomic ganglion
  • Postganglionic nerve fiber originates in a ganglion and terminates in smooth cardiac muscle or a gland
• Summary of Sympathetic and Parasympathetic NS:

  Sympathetic NS:

  • Origin: Thoraco-lumbar
  • Neurotransmitters: Norepinephrine or Noradrenaline, Epinephrine or Adrenaline
  • Response: "Fight or Flight"
  • Effects: Pupillary dilation, increased heart rate, force, and blood pressure
• Parasympathetic NS:

  • Origin: Cranio (III, VII, IX, X), Sacral (III, IV)
  • Neurotransmitter: Acetylcholine
  • Response: "Rest and Digest"